Sripan P.,Chiang Mai University |
Sripan P.,Institute Of Recherche Pour Le D Veloppement Ird Umi 174 |
Ngo-Giang-Huong N.,Institute Of Recherche Pour Le D Veloppement Ird Umi 174 |
Ngo-Giang-Huong N.,Chiang Mai University |
And 20 more authors.
Chiang Mai Journal of Science | Year: 2012
Exposure to single dose nevirapine during labor (SD-NVP) to prevent mother to child transmission of HIV (PMTCT) is associated with a lower likelihood of virologic suppression at six months of a nevirapine based antiretroviral therapy but long-term consequences of SD-NVP have not been studied. We analyzed data from women who received SD-NVP in the PHPT-2 PMTCT clinical trial. Following delivery, women initiated a regimen composed of nevirapine, lamivudine, and stavudine or zidovudine when their CD4 level declined to less than 250 cells/mm3. HIV RNA load and CD4 cell counts were evaluated every six months. Failure was defined as a confirmed HIV RNA load >400 copies/mL at least 6 months after therapy initiation, or death, and observations were censored at time of drop out or switch to a protease inhibitor based regimen. Survival analysis was performed using Kaplan-Meier estimates and Cox regression models. The 221 SD-NVP exposed women and 48 unexposed women had similar characteristics at baseline, except the time spent between delivery and initiation of therapy (6.1 and 14.9 months, respectively). At four years, 35% of the SD-NVP exposed and 14% of the unexposed women met the failure criteria (P=0.02). In the multivariable analysis, factors contributing to the failure consisted of exposure to SD-NVP (HR: 2.63, P=0.03), plasma HIV-1 RNA level above median (HR: 2.53, P<0.001), stage C of the CDC HIV clinical staging (HR: 2.12, P=0.04), platelets cell count above median (HR: 1.65, P=0.04) and early initiation of therapy after delivery (HR: 1.64, P=0.04). In this cohort, the impact of SD-NVP on further antiretroviral therapy was still significant after four years of therapy, justifying the use of strategies to prevent resistance mutations after exposure to SD-NVP.
Cressey T.R.,Chiang Mai University |
Cressey T.R.,Harvard University |
Cressey T.R.,CIRAD - Agricultural Research for Development |
Jourdain G.,Chiang Mai University |
And 16 more authors.
AIDS | Year: 2010
Objective: To evaluate the pharmacokinetics and HIV viral load response following initiation during the third trimester of pregnancy of zidovudine plus standard-dose lopinavir boosted with ritonavir (LPV/r), twice daily, until delivery for the prevention of mother-to-child transmission of HIV. Design: Prospective study nested within a multicenter, three-arm, randomized, phase III prevention of mother-to-child transmission of HIV trial in Thailand (PHPT-5, ClinicalTrials.gov Identifier: NCT00409591). Methods: Women randomized to receive 300 mg zidovudine and 400/100 mg LPV/r twice daily from 28 weeks gestation, or as soon as possible thereafter, until delivery had intensive steady-state 12-h blood sampling performed. LPV/r pharmacokinetic parameters were calculated using noncompartmental analysis. Rules were defined a priori for a LPV/r dose escalation based on the proportion of women with an LPV area under the concentration-time curve (AUC) below 52 μg h/ml (10th percentile for LPV AUC in nonpregnant adults). HIV-1 RNA response was assessed during the third trimester. Results: Thirty-eight women were evaluable; at entry, median (range) gestational age was 29 (28-36) weeks, weight 59.5 (45.0-91.6) kg, CD4 cells count 442 (260-1327) cells/μl and HIV-1 RNA viral load 7818 (<40-402 015) copies/ml. Geometric mean (90% confidence interval) LPV AUC, Cmax and Cmin were 64.6 (59.7-69.8) μg h/ml, 8.1 (7.5-8.7) μg/ml and 2.7 (2.4-3.0) μg/ml, respectively. Thirty-one of 38 (81%) women had an LPV AUC above the AUC target. All women had a HIV-1 viral load less than 400 copies/ml at the time of delivery. Conclusion: A short course of zidovudine plus standard-dose LPV/r initiated during the third trimester of pregnancy achieved adequate LPV exposure and virologic response. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Homkham N.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt |
Homkham N.,Chiang Mai University |
Homkham N.,Kasetsart University |
Homkham N.,University Paris Saclay |
And 24 more authors.
Pediatric Infectious Disease Journal | Year: 2015
In 188 HIV-infected children receiving efavirenz, a lower middose (C12) was associated with a higher risk of HIV-1 viral load >400 copies/ mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C12 below target threshold (<1.0 mg/L) with a 23% risk of viral replication. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Riyaten P.,Chiang Mai University |
Riyaten P.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt |
Salvadori N.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt |
Salvadori N.,Chiang Mai University |
And 29 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015
Background: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. Methods: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≤126 mg/dL or random plasma glucose ≤200 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. Results: Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of followup (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≤1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure≤1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. Conclusions: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Suaysod R.,Chiang Mai University |
Ngo-Giang-Huong N.,Chiang Mai University |
Ngo-Giang-Huong N.,Harvard University |
Salvadori N.,Chiang Mai University |
And 17 more authors.
Clinical Infectious Diseases | Year: 2015
Background: Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. Methods: HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. Results: A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P =. 03), age >13 years (aHR, 2.9; P <. 001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P =. 03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P <. 001). Conclusions: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © 2015 The Author 2015.